Molecular Diversity of Epstein‐Barr Virus IgG and IgA Antibody Responses in Nasopharyngeal Carcinoma: A Comparison of Indonesian, Chinese, and European Subjects

Abstract

Epstein-Barr virus (EBV)-specific immunoblot analysis was used to reveal the molecular diversity of immunoglobulin (Ig) G and IgA antibody responses against Epstein-Barr nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) in serum samples from patients with nasopharyngeal carcinoma (NPC) and control subjects, by use of immunofluorescence assay (IFA). Control donors (n=150) showed IgG responses to few EBV proteins--VCA-p18, VCA-p40, EBNA1, and Zebra--and sporadically weak IgA reactivity to EBNA1 and VCA-p18. Patients with NPC stage 1 (n=6) had similar response patterns. Patients with NPC stage 2-4 (n=132) showed significantly more diverse IgG and IgA responses to EA and VCA proteins--VCA-p18/-p40, EBNA1, Z-encoded broadly reactive activator, and EAd-p47/54, -DNAse, -thymidine kinase, and -p138. No correlation was found between IFA titers and the number of EBV proteins recognized by IgG or IgA. Our results reveal dissimilarity between EBV polypeptides recognized by IgG and IgA antibodies, which suggests independent B cell triggering events.

Noninvasive diagnosis of nasopharyngeal carcinoma: Nasopharyngeal brushings reveal high Epstein‐Barr virus DNA load and carcinoma‐specific viral BARF1 mRNA

“…2, Table I). Interestingly, the healthy carrier showed IgA reactivity to EBNA1 and VCA-p18, which is very characteristic for NPC patients, but is normally rarely observed in healthy EBV-carriers, 11 indicating putative aberrant EBV activity in this individual. We are now regularly examining this volunteer for EBV and clinical parameters.…”

“…11 Healthy controls were characterised by restricted IgG antibody diversity profiles with IgG antibodies to VCA-p18 and/or EBNA1, but rarely had EBV-specific IgA antibodies. NPC patients were characterised by positive IgG and IgA responses to VCA-p18 and EBNA1 epitopes and all had an abnormal IgG diversity profile on immunoblot, used as confirmatory test.…”

“…NPC patients were characterised by positive IgG and IgA responses to VCA-p18 and EBNA1 epitopes and all had an abnormal IgG diversity profile on immunoblot, used as confirmatory test. 11 …”

“…4 The strong etiological link between EBV and NPC has been known for over 3 decades [1][2][3]6 and is reflected by abnormal anti-EBV antibody profiles, increased circulating EBV DNA levels and by distinct EBV gene expression in the tumour cells. [7][8][9][10][11] Classically, NPC is considered to have a latency type 2 EBV transcription, with expression of EBV-encoded small RNAs 1 and 2 (EBER1/2), BamHI A rightward transcripts (BARTs), EpsteinBarr nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2), while LMP1 is more heterogeneously expressed. 2,12,13 Previously, we and others showed additional transcription of a viral oncogene encoded in the BamHI-A rightward frame 1 (BARF1).…”

“…Both IgG and IgA antibody responses to defined EBV proteins may be used as NPC markers. 11 Quantitation of circulating EBV DNA may be useful for prognostic monitoring in a subset of patients, 9 but because of low or negative EBV DNA values in a significant number of NPC patients, this method is less suited for primary diagnosis. 22 EBV DNA in the blood of NPC patients appears highly fragmented, reflecting tumour apoptosis or necrosis.…”